F.J. Huikeshoven (Frans)http://repub.eur.nl/ppl/6135/
List of Publicationsenhttp://repub.eur.nl/eur_signature.pnghttp://repub.eur.nl/
RePub, Erasmus University RepositoryRecurrent endometrial cancer: A retrospective studyhttp://repub.eur.nl/pub/36150/
Mon, 01 Jan 2007 00:00:01 GMT<div>F.H. van Wijk</div><div>F.J. Huikeshoven</div><div>L. Abdulkadir</div><div>P.C. Ewing</div><div>C.W. Burger</div>
Objective: The value of follow-up after treatment for endometrial cancer will be discussed. Study design: We evaluated our clinical experience, including mode of detection, of patients with recurrent endometrial cancer treated in the Erasmus Medical Centre in Rotterdam over a 20-year period. Clinical data and histopathological features from 64 patients were analyzed. Survival was analyzed with a Kaplan-Meier curve. Results: Twenty-two patients had a local recurrence, 30 had a distant recurrence and 12 had simultaneous local and distant recurrent disease. Ninety-five percent of the local recurrences and 67% of the distant recurrences were detected within three years. Twenty-seven patients had a screen-detected recurrence, 34 had an interval screening recurrence and two had a chance finding recurrence. The overall survival rate at two years was 70% and at five years 53%. Patients with a screen-detected recurrence had a 5-year survival rate of 62%, while patients with interval screening and chance finding recurrences had a 5-year survival rate of 47%. Conclusion: A follow-up program in the first three years after primary treatment of endometrial cancer is useful in detecting recurrent disease. We have no reason to use a different program of follow-up in patients with low risk primary disease. Stage III and IV endometrial cancer: A 20-year review of patientshttp://repub.eur.nl/pub/67881/
Sat, 01 Jul 2006 00:00:01 GMT<div>F. van Wijk</div><div>F.J. Huikeshoven</div><div>L. Abdulkadir</div><div>P.C. Ewing</div><div>C.W. Burger</div>
In advanced endometrial cancer, the importance of peritoneal cytology and optimal surgical cytoreduction remain subjects of discussion. We evaluated our clinical experience of 67 patients with FIGO stage III and IV endometrial cancer treated in the Erasmus Medical Centre in Rotterdam over a 20-year period with an emphasis on stage IIIA disease based on positive cytology only and optimal cytoreduction. Lymphadenectomy was not routinely performed and peritoneal cytology was examined in 74% of the patients. Stage IIIA disease was found in 33 patients, 10 of whom had positive cytology only. Analysis showed that incidence of recurrence and survival rates of patients with stage IIIA disease based on positive cytology only were comparable with stage IIIA disease based on other factors. In 50 patients, it was possible to remove all macroscopic tumor, whereas in 17 patients, an optimal cytoreduction was not achievable. The 2- and 5-year survival rates after optimal cytoreduction were 82.2% and 65.6%; where this could not be achieved, these figures were 50.8% and 40.6%. In advanced endometrial cancer patients, positive peritoneal cytology seems an important prognostic factor in stage IIIA disease if lymph node status is unknown. Survival is improved if optimal surgical cytoreduction is achievable.Growth regulation and transcriptional activities of estrogen and progesterone in human endometrial cancer cellshttp://repub.eur.nl/pub/65643/
Sun, 01 Jan 2006 00:00:01 GMT<div>S.C.J.P. Gielen</div><div>E.E. Hanekamp</div><div>P. Hanifi-Moghaddam</div><div>A.M. Sijbers</div><div>A.J. van Gool</div><div>C.W. Burger</div><div>L.J. Blok</div><div>F.J. Huikeshoven</div>
Estrogen-stimulated growth of the malignant human endometrium can be balanced by the differentiating properties of progesterone. To study the molecular basis behind this, gene expression profiling was performed using complementary DNA microarray analysis. In this study, the human endometrial cancer cell lines ECC-1 and PRAB-36 were used as models. The ECC-1 cell line, which expresses high levels of estrogen receptor α and is stimulated in growth by estrogens, was used to study estrogen regulation of gene expression. The Ishikawa sub-cell line PRAB-36, expressing both PRA and PRB, progesterone receptor isoforms, and inhibited in growth by progestagens, was used to study progesterone regulation of gene expression. Using these two well-differentiated human endometrial cancer cell lines, 148 estrogen- and 148 progesterone- regulated genes were identified. After functional classification, the estrogen- and progesterone-regulated genes could be categorized in different biologically relevant groups. Within the group of "cell growth and/or maintenance," 81 genes were clustered, from which a number of genes could be involved in arranging the cross talk that exists between estrogen and progesterone signaling. On the basis of analysis of the current findings, it is hypothesized that cross talk between estrogen and progestagen signaling does not occur by counterregulation of single genes, but rather at the level of differential regulation of different genes within the same functional families.Differences in invasive capacity of endometrial cancer cell lines expressing different progesterone receptor isotypes: possible involvement of cadherinshttp://repub.eur.nl/pub/15102/
Sun, 01 May 2005 00:00:01 GMT<div>E.E. Hanekamp</div><div>S.C.J.P. Gielen</div><div>P.E. de Ruiter</div><div>S. Chadha-Ajwani</div><div>F.J. Huikeshoven</div><div>C.W. Burger</div><div>J.A. Grootegoed</div><div>L.J. Blok</div>
OBJECTIVE: Loss of expression of progesterone receptors (PR) in endometrial cancer is related to a more invasive and metastatic phenotype. In this study we aim to investigate whether selective loss of PRA or PRB affects the invasive capacity of endometrial cancer cells. METHODS: cDNA microarrays were performed to compare gene expression profiles of a set of endometrial cancer sub-cell lines expressing PRA and/or PRB. In vitro invasion assays were performed to assess whether differences in gene expression between the lines were reflected by their invasive behavior. RESULTS: It was observed that cell lines that express only PRA express higher levels of cadherins, and show a lower level of invasion compared to cell lines that express PRB. When cadherin function was inhibited in exclusively PRA-expressing cell lines, an increase of in vitro invasion was observed. In support of these findings, it was observed that in higher grade and more invasive endometrial cancer, expression of E-cadherin decreased. CONCLUSIONS: These results indicate that relative loss of PRA during progression of endometrial cancer can have a negative impact on cadherin expression, which may lead to development of a more metastatic phenotype.Progesterone-induced inhibition of growth and differential regulation of gene expression in PRA- and/or PRB-expressing endometrial cancer cell lineshttp://repub.eur.nl/pub/68421/
Sun, 01 May 2005 00:00:01 GMT<div>E. Smid-Koopman</div><div>F.J. Huikeshoven</div><div>L.J. Blok</div><div>L.C. Kühne</div><div>E.E. Hanekamp</div><div>S.C.J.P. Gielen</div><div>P.E. de Ruiter</div><div>J.A. Grootegoed</div><div>T.J.M. Helmerhorst</div><div>C.W. Burger</div><div>A.O. Brinkmann</div>
OBJECTIVE: Progesterone plays an important role in controlling proliferation and differentiation of the human endometrium. Because there are two progesterone receptor isoforms (PRA and PRB), it was important to generate tools to be able to study the role of these two progesterone receptors separately. METHODS: Using stable transfection techniques, both human progesterone receptor isoforms (hPRA and hPRB) were reintroduced into a hPR-negative subclone of the well-differentiated endometrial cancer cell line Ishikawa. Several Ishikawa subcell lines were constructed, each expressing different levels of hPRA, hPRB, or hPRA and hPRB, respectively. RESULTS: These Ishikawa subcell lines showed a marked progesterone-induced growth inhibition with induction of apoptosis after long-term culture in the presence of hormone. Upon measuring gene regulation, a clear difference in regulation of expression of the selected genes by progesterone treatment was observed between the PRA-, PRB-, or PRA/B-expressing cell lines. Integrin β4 (ITGB4) was only regulated in PRA-expressing cells; amphiregulin was highly regulated in PRB-expressing cells; inuslin-like gwoth factor binding protein 3 (IGFBP3) was only regulated in PRB- and PRA/B-expressing cells; and metallothionein 1L (MT1L) was highly regulated in PRA/B-expressing cells. Interestingly, based on literature data, these genes can be implicated in induction of apoptosis, but are modulated here in such a way that suggests induction of resistance against apoptosis. CONCLUSION: Reintroduction of PRs into Ishikawa cells rescued progesterone responsiveness in these cells. Furthermore, using these human endometrial cancer subcell lines, clear and distinct functional differences between the PR isoforms were observed. CopyrightSteroid-modulated proliferation of human endometrial carcinoma cell lines: Any role for insulin-like growth factor signaling?http://repub.eur.nl/pub/67273/
Sat, 01 Jan 2005 00:00:01 GMT<div>S.C.J.P. Gielen</div><div>E.E. Hanekamp</div><div>L.J. Blok</div><div>F.J. Huikeshoven</div><div>C.W. Burger</div>
Estrogen-stimulated proliferation of the normal and malignant human endometrium is balanced by the differentiating properties of progesterone. This study evaluated the role of insulin-like growth factor (IGF) signaling in steroid-induced modulation of endometrial cancer cell proliferation. We used the human endometrial, estrogen-responsive ECC-1 and progesterone-responsive PRAB-36 cell lines. Proliferation studies with IGFs in combination with either estrogen or progesterone were conducted. Furthermore, the mRNA and protein expression of insulin-like growth factor-binding proteins (IGFBPs) was evaluated. Using the ECC-1 cell line, we observed that estrogen-induced proliferation is modulated via the IGF-receptor signaling pathway, and that IGF-1-induced stimulation of proliferation does not influence estrogen receptor signaling. Furthermore, expression of the main modulators of IGF action, the IGFBPs, was found to be regulated by estrogen and progesterone in both cell lines. IGFBP-4 was up-regulated by estrogen in the ECC-1 cell line, and IGFBP-3 and IGFBP-6 were down-regulated by progesterone in the PRAB-36 cell line. Estrogen-induced stimulation of proliferation of ECC-1 endometrial cancer cells is partly achieved via IGF signaling. Furthermore, the IGFBPs are regulated by estrogens as well as progestagens and could potentially play a role in the modulation of endometrial cancer cell proliferation. CopyrightGene expression profiling in human endometrial cancer tissue samples: Utility and diagnostic valuehttp://repub.eur.nl/pub/73022/
Sat, 01 May 2004 00:00:01 GMT<div>E. Smid-Koopman</div><div>L.J. Blok</div><div>T.J.M. Helmerhorst</div><div>S. Chadha-Ajwani</div><div>C.W. Burger</div><div>A.O. Brinkmann</div><div>F.J. Huikeshoven</div>
Objective. Recently, gene expression profiling techniques have been used on several human cancers to classify tumor subgroups with a specific biological behavior, which were previously undetected by the conventional histopathologic staging systems. In the current study, the clinical usefulness and prognostic value of gene expression profiling in human endometrial carcinomas were studied. Methods. A macro cDNA array, containing cDNAs of 588 genes selected from different areas of cancer research, was used to generate gene expression profiles of tumor tissue samples. The gene expression profiles of 12 endometrial cancers, 3 benign (e.g. noncancer) endometrial tissue samples and 3 myometrial tissue samples, taken from human surgical specimen, were compared. Results. The efficacy to generate a gene expression profile of these tissue samples was 77%. The RNA samples could be randomly taken from the tissue samples and were highly reproducible. Cluster analysis of gene expression profiles of the different samples showed that the benign endometrial and the myometrial samples clustered separately from the tumor samples, indicating that the gene expression profiles were tissue specific and not patient specific. Cluster analysis of the tumor samples revealed two distinct tumor clusters. Ranking of the tumors in the two clusters showed high similarity with the histopathologic classification [International Federation of Gynecology and Obstetrics (FIGO) grading]. Conclusion. Classification of endometrial tumors on basis of their gene expression profiles showed similarity with the FIGO grading system.Progesterone receptors in endometrial cancer invasion and metastasis: Development of a mouse modelhttp://repub.eur.nl/pub/63544/
Sat, 01 Nov 2003 00:00:01 GMT<div>E.E. Hanekamp</div><div>S.C.J.P. Gielen</div><div>S.A. van Oosterhoud</div><div>C.W. Burger</div><div>J.A. Grootegoed</div><div>F.J. Huikeshoven</div><div>L.J. Blok</div>
Progestagens inhibit growth of endometrial cancer cells in vivo and in vitro, and also are reported to inhibit endometrial cancer cell invasion. The progesterone receptor (PR) isotypes PRA and PRB have different transcriptional activity. There are indications that relative over expression of PRB could lead to development of a more invasive phenotype in endometrial cancer. To study the effect of progestagens and the two PR isotypes on tumor dissemination, in vitro and in vivo models should be applied. The Ishikawa endometrial cancer cell line (clone 3H12) was transfected to stably express a high level of human PRB (hPRB), which resulted in the PRB-1 sub-cell line. Ovariectomized athymic NMRI nu/nu mice were injected intraperitoneally with these PRB-1 cells. After 3, 5 and 10 weeks, the animals were sacrificed. Spread of PRB-1 cells in and outside the peritoneal cavity was studied macroscopically and microscopically, and also by PCR detection. After 10 weeks, the PRB-1 cells had formed extensive tumor mass in the peritoneal cavity. Also, cells could be detected outside the peritoneal cavity, indicating metastatic ability of these cells. The present study describes an in vivo model that can provide a valuable tool in studying the influence of progestagens and the two PR isotypes on endometrial cancer cell invasion and metastasis.Consequences of loss of progesterone receptor expression in development of invasive endometrial cancerhttp://repub.eur.nl/pub/10230/
Wed, 01 Jan 2003 00:00:01 GMT<div>E.E. Hanekamp</div><div>L.J. Blok</div><div>S.C.J.P. Gielen</div><div>E. Smid-Koopman</div><div>L.C. Kühne</div><div>P.E. de Ruiter</div><div>S. Chadha-Ajwani</div><div>A.O. Brinkmann</div><div>J.A. Grootegoed</div><div>C.W. Burger</div><div>F.J. Huikeshoven</div>
PURPOSE: In endometrial cancer, loss of progesterone receptors (PR) is
associated with more advanced disease. This study aimed to investigate the
mechanism of action of progesterone and the loss of its receptors (PRA and
PRB) in development of endometrial cancer. EXPERIMENTAL DESIGN: A
9600-cDNA microarray analysis was performed to study regulation of gene
expression in the human endometrial cancer subcell line Ishikawa PRAB-36
by the progestagen medroxy progesterone acetate (MPA). Five MPA-regulated
genes were selected for additional investigation. Expression of these
genes was studied by Northern blot and by immunohistochemistry in Ishikawa
subcell lines expressing different PR isoforms. Additionally, endometrial
cancer tissue samples were immunohistochemically stained to study the in
vivo protein expression of the selected genes. RESULTS: In the PRAB-36
cell line, MPA was found to regulate the expression of a number of
invasion- and metastasis-related genes. On additional investigation of
five of these genes (CD44, CSPG/Versican, Tenascin-C, Fibronectin-1, and
Integrin-beta 1), it was observed that expression and progesterone
regulation of expression of these genes varied in subcell lines expressing
different PR isoforms. Furthermore, in advanced endometrial cancer, it was
shown that loss of expression of both PR and E-cadherin was associated
with increased expression CD44 and CSPG/Versican. CONCLUSION: The present
study shows that progestagens exert a modulatory effect on the expression
of genes involved in tumor cell invasion. As a consequence, loss of PR
expression in human endometrial cancer may lead to development of a more
invasive phenotype of the respective tumor.Distinct functional differences of human progesterone receptors A and B on gene expression and growth regulation in two endometrial carcinoma cell lineshttp://repub.eur.nl/pub/74288/
Wed, 01 Jan 2003 00:00:01 GMT<div>E. Smid-Koopman</div><div>L.J. Blok</div><div>L.C. Kühne</div><div>C.W. Burger</div><div>T.J.M. Helmerhorst</div><div>A.O. Brinkmann</div><div>F.J. Huikeshoven</div>
Objective: To study the functional differences between the two progesterone receptor isoforms (hPRA and hPRB) in human endometrial cancer, two new endometrial carcinoma cell lines were created - one expressing hPRA and one expressing hPRB. Methods: A well-differentiated, hPR-negative Ishikawa cell line was stably transfected with either hPRA or hPRB cDNA. Transfected cells were selected, and two cell lines expressing approximately equal amounts of receptor were isolated - one expressing hPRA (PRA-14) and one expressing hPRB (PRB-59). Results: Cell growth experiments revealed a growth-inhibitory response to progestins (MPA and R5020) in the PRB-59 cells but not in the PRA-14 cells. Differences in expression of genes targeted by the two isoforms were studied using a cDNA expression array technique. A different set of genes appeared to be progesterone regulated in the PRA-14 cells than in the PRB-59 cells. None of the genes were regulated by both hPRA and hPRB. Insulin-like growth factor binding protein 3 expression was studied in more detail as an example of a gene regulated in PRB-59 cells but not in PRA-14 cells. Conclusion: We established a new model to study functional differences between the two hPR isoforms in human endometrial carcinoma cells. This model revealed distinctive differences in target gene regulation between the two hPR isoforms. Moreover, antiproliferative actions of progesterone on human endometrial cancer cells could be observed only in the PRB-expressing cell line. CopyrightMassive solitary metastasis of hepatocellular carcinoma in the ovary two years after liver transplantationhttp://repub.eur.nl/pub/63705/
Mon, 01 May 2000 00:00:01 GMT<div>M.E. de Groot</div><div>L. Dukel</div><div>S. Chadha-Ajwani</div><div>H.J. Metselaar</div><div>H.W. Tilanus</div><div>F.J. Huikeshoven</div>
Differential gene expression in progesterone-sensitive and progesterone-insensitive endometrial carcinoma cellshttp://repub.eur.nl/pub/64309/
Mon, 01 Feb 1999 00:00:01 GMT<div>E. Koopman</div><div>L.J. Blok</div><div>A.O. Brinkmann</div><div>T.J.M. Helmerhorst</div><div>F.J. Huikeshoven</div>
The low transverse Pfannenstiel incision and the prevalence of incisional hernia and nerve entrapmenthttp://repub.eur.nl/pub/58778/
Mon, 01 Dec 1997 00:00:01 GMT<div>R.W. Luijendijk</div><div>J. Jeekel</div><div>R.K. Storm</div><div>P.J. Schutte</div><div>W.C.J. Hop</div><div>A.C. Drogendijk</div><div>F.J. Huikeshoven</div>
Dinoprostone priming of the cervix prior to termination of midgestation pregnancy with sulprostonehttp://repub.eur.nl/pub/71707/
Fri, 23 Jun 1995 00:00:01 GMT<div>C.C.Th. Rietberg</div><div>F.K. Lotgering</div><div>F.J. Huikeshoven</div>
Objective: To determine if cervical ripening with the prostaglandin E2 analogue dinoprostone effectively shortens the induction-to-delivery interval in midpregnancy terminations with sulprostone. Study design: We retrospectively studied 100 women admitted for pregnancy termination at midgestation because of fetal anomalies between September 1989 and January 1993. Three regimens were used: 27 women received intramuscular sulprostone only, 29 women received intravenous sulprostone only, and 44 women received intravenous sulprostone after cervical priming with dinoprostone. Wilcoxon's rank sum test was used for statistical analysis. Results: Dinoprostone priming did not significantly reduce the induction-to-delivery interval in either parous or nulliparous women. However, when divided into first and subsequent pregnancies, we found that primigravidae, but not multigravidae, had an induction-to-delivery interval that was significantly shorter by approximately 10.5 h when pretreated with dinoprostone. Conclusion: Dinoprostone priming of the cervix prior to termination of midgestation pregnancy with sulprostone (Nalador) effectively shortens the induction-to-delivery interval in women in their first pregnancy.Conus-cauda syndrome as a presenting symptom of endodermal sinus tumor of the ovaryhttp://repub.eur.nl/pub/59337/
Mon, 10 Apr 1995 00:00:01 GMT<div>J. den Boon</div><div>C.J.J. Avezaat</div><div>A. van der Gaast</div><div>W. Koops</div><div>F.J. Huikeshoven</div>
We report on a case of a 46-year-old woman with a conus-cauda syndrome due to an endodermal sinus tumor of the right ovary with multiple metastases in the spine and pelvic bone. Before removing the tumor surgically, combination chemotherapy was given to treat the metastases, which threatened to compromise the spinal cord.Androgen receptor expression in human ovarian and uterine tissue of long term androgen-treated transsexual womenhttp://repub.eur.nl/pub/56768/
Wed, 23 Nov 1994 00:00:01 GMT<div>D. Chadha</div><div>T.D. Pache</div><div>F.J. Huikeshoven</div><div>A.O. Brinkmann</div><div>Th.H. van der Kwast</div>
Androgen receptor (AR) modulation in human uteri and ovaries of long term androgen-treated transsexual female patients was investigated. Androgen receptor expression was evaluated immunohistochemically in the ovaries of 11 and the endometria and myometria of six androgen-treated transsexual female patients. This was compared with AR expression in the ovaries and uteri of premenopausal and postmenopausal women not receiving treatment and in 10 ovaries of female patients with polycystic ovarian disease (PCOD). In the normal ovaries germinal epithelium, granulosa cells of antral follicles, corpus luteum, and thecal and stromal cells exhibited moderate AR expression. The more intense and uniform staining of ovarian stroma of female transsexual patients and those of patients with PCOD compared with ovarian stroma of normal controls was most remarkable. This similarity in histology and distribution of ARs supports the hypothesis that PCOD is an androgen-mediated disorder. Immunostaining for ARs was only occasionally detectable in the uteri of premenopausal and postmenopausal women. In contrast, myometrial and endometrial stroma of the uteri of female transsexual patients displayed an intense and diffuse nuclear immunostaining, but glandular epithelia remained unstained. Western blot analysis of the ovaries and uterine myometrial tissue samples from transsexual female patients confirmed the presence of the 110-kd AR molecule. Because the androgen treatment of some transsexual female patients was discontinued 6 weeks before they underwent hysterosalpingo-oophorectomy, our data indicate a stable and persistent androgen-induced up-regulation of AR expression in ovaries.The occurrence of diversion colitis in patients with a sigmoid neovaginahttp://repub.eur.nl/pub/63159/
Wed, 25 Aug 1993 00:00:01 GMT<div>T.A. Toolenaar</div><div>I. Freundt</div><div>F.J. Huikeshoven</div><div>A.C. Drogendijk</div><div>J. Jeekel</div><div>S. Chadha-Ajwani</div>
Diversion colitis is an inflammatory process occurring in segments of the colorectum surgically diverted from the fecal stream. Clinical symptoms of this condition are rectal discomfort, pain, discharge, and bleeding. We diverted isolated segments of sigmoid to create neovaginas in patients with aplasia vaginae and in male to female transsexuals. In contrast to what is reported in most studies of diversion colitis, the neovagina consists of an isolated segment not connected to the anus in patients without any pre-existing bowel disease. To investigate the occurrence of diversion colitis in these sigmoid-neovaginas we studied biopsy specimens from 13 patients. Most of the patients complained of discharge and slight blood loss from their sigmoid-neovagina. Microscopic examination of the biopsy specimens showed lymphocytic infiltration in all cases. Four cases showed an acute inflammatory infiltrate in the lamina propria. Our results indicate that the changes observed on clinical and histopathologic examinations represent the entity of mild diversion colitis. We conclude that diversion colitis also occurs in a sigmoid neovagina.Bacterial flora of the sigmoid neovaginahttp://repub.eur.nl/pub/8599/
Fri, 01 Jan 1993 00:00:01 GMT<div>T.A. Toolenaar</div><div>I. Freundt</div><div>J.H. Wagenvoort</div><div>F.J. Huikeshoven</div><div>M. Vogel</div><div>J. Jeekel</div><div>A.C. Drogendijk</div>
The bacterial microbiota of 15 sigmoid neovaginas, created in patients
with congenital vaginal aplasia or male transsexualism, was studied. No
specimen was sterile, and only normal inhabitants of the colon were
cultured. The total counts of bacteria were lower than those reported for
healthy sigmoid colons.